Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma
Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma
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DOI：
10.1158/0008-5472.can-05-3840
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发表时间：
2006-05-01
期刊：
影响因子：
11.2
通讯作者：
Yasumoto, Kosei
中科院分区：
文献类型：
--
作者：
Fukuyama, Takashi;Hanagiri, Takeshi;Yasumoto, Kosei
本研究的目的是鉴定一种能够在肺癌患者中诱导特异性细胞免疫应答的肿瘤特异性抗原。我们建立了一个肺腺癌细胞系，命名为F1121 L，并从患者F1121的局部淋巴结淋巴细胞中诱导肿瘤特异性CTL克隆HI。CTL克隆H1以HLA-B*1507限制性方式裂解自体肿瘤细胞，但不裂解自体EBV-B、植物血凝素母细胞和K562。CTL克隆还以HLA限制性方式识别同种异体HLA-B*1501-或1507-阳性肺癌细胞系。利用CTL克隆，我们通过cDNA表达克隆技术鉴定了抗原编码基因。该基因全长556 bp，包括一个由113个氨基酸组成的开放阅读框架，命名为KK-LC-1。9-mer肽（KK-LC-1（76-84）; RQKRILVNL）被鉴定为表位肽。该抗原的基因组DNA位于染色体Xq 22上。逆转录-PCR分析表明，该基因的mRNA仅在正常组织中的睾丸表达。在18个同种异体非小细胞肺癌细胞系中有9个（50%）表达，在100个非小细胞肺癌组织中有40个（40%）表达。因此，我们确定了一个新的肿瘤抗原编码基因分类为癌症/生殖系基因的自体肺癌和CTL系统。新的癌/生殖系基因位于Xq 22，这显然不同于以前报道的癌/生殖系基因的位置。
The purpose of our present study is to identify a tumor-specific antigen capable of inducing a specific cellular immune response in lung cancer patients. We established a lung adenocarcinoma cell line, designated as F1121L, and induced tumor-specific CTL clone HI from regional lymph node lymphocytes of patient F1121. CTL clone HI lysed autologous tumor cells in an HLA-B*1507-restricted manner, but not autologous EBV-B, phytohemagglutinin-blast cells, and K562. The CTL clone also recognized allogencic HLA-B*1501- or 1507-positive lung cancer cell lines in the HLA-restricted manner. Using the CTL clone, we identified an antigen-coding gene by cDNA expression cloning technique. The gene consisted of 556 bp, including an open reading frame consisted of 113 amino acids, designated as Kita-kyushu lung cancer antigen 1 (KK-LC-1). A 9-mer peptide (KK-LC-1(76-84); RQKRILVNL) was identified as an epitope peptide. The genomic DNA of this antigen was located in chromosome Xq22. A reverse transcription-PCR analysis revealed that the mRNA of this gene was only expressed in the testis among normal tissues. It was expressed in 9 of 18 (50%) allogeneic non-small-cell lung cancer cell lines and in 40 of 100 (40%) non-small-cell lung cancer tissues. We thus identified a new tumor antigen-coding gene categorized as a cancer/germline gene by an autologous lung cancer and CTL system. The new cancer/germline gene was located in Xq22, which is apparently different from the locations of previously reported cancer/germline genes.